Muscarinic M1, M3, Nicotinic,GABAA and GABAB Receptor ...

achieving optimal blood sugar control. Recent therapeutic strategies aimed at
closely controlling elevated glucose levels in diabetic individuals put them at risk
for experiencing episodes of hypoglycemia. Reports suggest that if intensive
insulin therapy is to be used, great effort must be taken to avoid hypoglycemia
(Bilotta et al., 2008). Acute and recurrent hypoglycemia cause transient or
persistent alteration of cognitive functions and result in seizures or coma. The
pathogenesis of hypoglycemia induced cognitive and functional deficit is largely
unknown, but mechanisms that could result in damage to cells of the CNS include
deregulation in neurotransmitter signaling. To understand the effects of
hypoglycemia on the cells of the CNS, it is essential to characterize the response
of CNS cells to reduced glycemic levels, to determine the extent of CNS cell
injury induced by hypoglycemia and to identify the mechanisms involved in
hypoglycemia induced cell or tissue damage in brain. Identification of neuronal
damage caused by neurotransmitter variations provides a better understanding of
the neurochemical mechanisms responsible for hypoglycemia associated deficit in
cognitive and behavioural response. The reports so far stated did not attempt to
emphasis the functional role of muscarinic, nicotinic and GABAergic receptor
subtypes in hypoglycemic and hyperglycemic brain.
Phospholipase C (PLC) is a key enzyme in phosphatidyl inositol turnover
and generates two second messengers, inositol 1,4,5-bisphosphate (IP3) and
diacylglycerol (DAG) from phosphatidyl inositol 4,5-bisphosphate [PI(4,5)P2] in
response to activation of receptors by hormones, neurotransmitters, growth
factors, and other molecules. IP3 induces calcium mobilization and DAG induces
activation of protein kinase C. PI(4,5)P2 is a substrate for PLC, and PI 3- kinase.
In addition, PI(4,5)P2 directly regulates a variety of cellular functions, including
cytoskeletal reorganization, exocytosis and channel activity. Therefore, strict
regulation of PI(4,5)P2 levels by PLC or other converting enzymes is necessary
for homeostasis (Fukami, 2002). Disruption of the cyclic AMP response element
binding (CREB) protein expression and its activity is associated with
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